Article
Medicine, Research & Experimental
Weibo Feng, Wenjie Huang, Jie Chen, Chenyang Qiao, Danfei Liu, Xiaoyu Ji, Meng Xie, Tongyue Zhang, Yijun Wang, Mengyu Sung, Dean Tian, Daiming Fan, Yongzhan Nie, Kaichun Wu, Limin Xia
Summary: HOXB5 gene plays a crucial role in promoting colorectal cancer metastasis by transactivating metastatic related genes CXCR4 and ITGB3. Additionally, a positive feedback loop of CXCL12-HOXB5-CXCR4 has been identified to have an important role in colorectal cancer metastasis.
Article
Oncology
Meggy Suarez-Carmona, Anja Williams, Jutta Schreiber, Nicolas Hohmann, Ulrike Pruefer, Juergen Krauss, Dirk Jaeger, Anna Froemming, Diana Beyer, Dirk Eulberg, Jarf Ulf Jungelius, Matthias Baumann, Aram Mangasarian, Niels Halama
Summary: The combination of CXCL12 inhibition and checkpoint inhibition is safe in patients with advanced colorectal and pancreatic cancer, showing promising results in prolonging time on trial treatment and inducing Th1-like tissue reactivity upon CXCL12 inhibition. Systematic serial biopsies revealed distinct patterns of modulation in tissue responses, while T cells showed directed movement towards tumor cells in responding tissues. Serum analyses detected homogeneous immunomodulatory patterns in all patients, suggesting further exploration of synergistic combinatorial strategies.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Pharmacology & Pharmacy
Guowen Lu, Yier Qiu, Xiaobao Su
Summary: Insufficient T cell infiltration in triple-negative breast cancer (TNBC) has led to limited responses to immune checkpoint blockade (ICB) therapies, prompting the development of immunostimulatory approaches. A novel CXCR4-targeted liposomal formulation was developed to enhance the therapeutic efficacy of AMD3100, a CXCR4 antagonist, leading to improved immune activation and antitumor effects in a murine TNBC model when combined with anti-PD-L1 therapy.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2021)
Article
Gastroenterology & Hepatology
Jin Huang, Pan Chen, Ke Liu, Jiao Liu, Borong Zhou, Runliu Wu, Qiu Peng, Ze-Xian Liu, Changfeng Li, Guido Kroemer, Michael Lotze, Herbert Zeh, Rui Kang, Daolin Tang
Summary: Inhibition of CDK1/2/5 kinase activity can overcome IFNG-mediated immune evasion in pancreatic tumors, turning a 'cold' tumor microenvironment into a 'hot' one and significantly improving overall survival rates in mouse pancreatic tumor models. Abnormal expression of CDK1/2/5 and IDO1 is associated with poor patient survival in various cancer types, including PDAC.
Article
Oncology
Nicholas J. Mullen, Ravi Thakur, Surendra K. Shukla, Nina Chaika, Sai Sundeep Kollala, Dezhen Wang, Chunbo He, Yuki Fujii, Shikhar Sharma, Scott E. Mulder, David B. Sykes, Pankaj K. Singh
Summary: In this study, we identified CNX-774 as a previously uncharacterized ENT1 inhibitor that could sensitize pancreatic cancer cell lines to the DHODH inhibitor brequinar (BQ). Our results also suggest that N-acetylneuraminic acid accumulation could serve as a potential marker for the therapeutic efficacy of DHODH inhibitors.
Article
Chemistry, Multidisciplinary
Kaixuan Zeng, Weihao Li, Yue Wang, Zifei Zhang, Linjie Zhang, Weili Zhang, Yue Xing, Chi Zhou
Summary: This study identifies CDK1 as a critical contributor to oxaliplatin resistance in colorectal cancer (CRC) by suppressing ferroptosis. CDK1 is highly expressed in oxaliplatin-resistant cells and tissues due to the loss of N6-methyladenosine modification. Inhibition of CDK1 restores sensitivity to oxaliplatin in CRC cells and xenograft models. Mechanistically, CDK1 phosphorylates and promotes ubiquitination of ACSL4, leading to its degradation and subsequent inhibition of lipid peroxidation and ferroptosis. These findings suggest that CDK1 inhibition may be a promising strategy for treating oxaliplatin-resistant CRC.
Article
Pharmacology & Pharmacy
Ye Li, Yuncang Yuan, Fan Zhang, Aizhen Guo, Fuao Cao, Mengmeng Song, Yating Fu, Xiaowen Xu, Hao Shen, Shangyong Zheng, Yamin Pan, Wenjun Chang
Summary: Our study found that frequent resistance to SHP2 inhibitors exists in colorectal carcinoma cells, even in those without RAS mutations. Rapid adaptive reactivation of the AKT pathway in response to SHP2 inhibition may contribute to this resistance, driven by the reactivation of RTKs or released p-FAK. Co-inhibition of FAK abrogated the feedback reactivation of AKT in response to SHP2 inhibition, leading to sustained AKT pathway suppression and improved antitumor efficacy.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Oncology
Deepak Rohila, In Hwan Park, Timothy Pham, Jonathan Weitz, Tatiana Hurtado de Mendoza, Suresh Madheswaran, Mehreen Ishfaq, Cooper Beaman, Elisabette Tapia, Siming Sun, Jay Patel, Pablo Tamayo, Andrew M. Lowy, Shweta Joshi
Summary: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease with limited treatment options. This study demonstrates that targeting macrophage spleen tyrosine kinase (Syk) can reprogram protumorigenic macrophages to an immunostimulatory phenotype, enhance CD8+ T-cell responses, and improve gemcitabine efficacy in PDAC.
Article
Chemistry, Multidisciplinary
Zhaoliang Yu, Peng Deng, Yufeng Chen, Shini Liu, Jinghong Chen, Zihuan Yang, Jianfeng Chen, Xinjuan Fan, Peili Wang, Zerong Cai, Yali Wang, Peishan Hu, Dezheng Lin, Rong Xiao, Yifeng Zou, Yan Huang, Qiang Yu, Ping Lan, Jing Tan, Xiaojian Wu
Summary: Dysregulation of the cell cycle machinery is a hallmark of colorectal cancer, with aberrant PLK1 signaling associated with recurrence and poor prognosis. Blocking PLK1 genetically and pharmacologically increases sensitivity to oxaliplatin. CDC7 is identified as a critical downstream effector of PLK1 signaling and its inhibitor enhances the anti-tumor effect of oxaliplatin in CRC models.
Article
Cell Biology
Xiaohui Shen, Yuchen Zhang, Zhuoqing Xu, Han Gao, Wenqing Feng, Wenchang Li, Yiming Miao, Zifeng Xu, Yaping Zong, Jingkun Zhao, Aiguo Lu
Summary: This study demonstrated that ML264 can restore oxaliplatin sensitivity in CRC PDOs by restoring the apoptotic response. KLF5 may be a potential therapeutic target for oxaliplatin-resistant CRC. PDOs have a strong potential for evaluating inhibitors and drug combination therapy in a preclinical environment.
CELL DEATH & DISEASE
(2022)
Article
Oncology
Yinghui Zhao, Chuanxin Wang, Ajay Goel
Summary: The study indicates that andrographis can reverse resistance to 5FU, highlighting its potential role in the treatment of colorectal cancer.
Article
Oncology
Varintra E. Lander, Jad I. Belle, Natalie L. Kingston, John M. Herndon, Graham D. Hogg, Xiuting Liu, Liang- Kang, Brett L. Knolhoff, Savannah J. Bogner, John M. Baer, Chong Zuo, Nicholas C. Borcherding, Daniel P. Lander, Cedric Mpoy, Jalen Scott, Michael Zahner, Buck E. Rogers, Julie K. Schwarz, Hyun Kim, David G. DeNardo
Summary: The effects of radiotherapy on tumor immunity in pancreatic ductal adenocarcinoma are not well understood. In this study, FAK inhibition was found to prime tumor immunity and unlock responsiveness to checkpoint immunotherapy in combination with radiotherapy.
Review
Biochemistry & Molecular Biology
Shiu-Jau Chen, Shao-Cheng Wang, Yuan-Chuan Chen
Summary: Immunotherapy is a novel anti-cancer method that provides a better or alternative option for cancer patients. While increasingly approved for cancer treatment, it still has limitations such as low response rates in most cases. Future development should focus on biomarker discovery, new tumor targets, neoadjuvant immunotherapy, and combination with conventional therapies for more effective outcomes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Immunology
Jiao-Ting Chen, Yu-Wen Zhou, Ting-Rui Han, Jun-Lun Wei, Meng Qiu
Summary: Surgical resection is essential for achieving good prognoses in colorectal cancer (CRC), but some patients fail to meet surgical indications or achieve pathological complete response after surgery. Perioperative therapy can effectively decrease tumor staging and reduce recurrence and metastasis. Immune checkpoint inhibitors (ICIs) have shown satisfactory efficacy and safety in patients with high microsatellite instability/deficient mismatch repair (MSI-H/dMMR), while the therapeutic effect is minimal in patients with mismatch repair-proficient or microsatellite stable (pMMR/MSS). Additional predictors are needed to screen patients with potential clinical benefits. Different combinations of immunotherapy in perioperative clinical trials for CRC have been comprehensively summarized in this review, focusing on efficacy and safety, and pointing out future directions.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Cell Biology
Hong-Bo Li, Zi-Han Yang, Qing-Qu Guo
Summary: Pancreatic cancer is a highly malignant tumor with poor therapeutic outcomes, and immune checkpoint inhibitors have limited efficacy in treating PDAC due to its inhibitory immune microenvironment. Strategies to enhance the efficacy of ICIs in PDAC treatment by targeting the tumor microenvironment are currently being explored.
CELL COMMUNICATION AND SIGNALING
(2021)
